ArticleSpringerPlus2014
Inhibition of neutral sphingomyelinases in skeletal muscle attenuates fatty-acid induced defects in metabolism and stress.
Article in SpringerPlus, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Muscle sphingolipids during rest and exercise: a C18:0 signature for insulin resistance in humans.Diabetologia · 2016Trial
- Dietary sphingolipids and milk fat globule membrane: emerging roles in cardiometabolic health and muscle function.Food science and biotechnology · 2025Review
- β2-Adrenergic Regulation of the Neuromuscular Transmission and Its Lipid-Dependent Switch.Molecular neurobiology · 2024Article
- The Role of Neutral Sphingomyelinase-2 (NSM2) in the Control of Neutral Lipid Storage in T Cells.International journal of molecular sciences · 2024Article
- Integrated lipids biomarker of the prediabetes and type 2 diabetes mellitus Chinese patients.Frontiers in endocrinology · 2022Article
- Neutral sphingomyelinase-2 and cardiometabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2021Review
- Ceramide and Sphingosine 1-Phosphate in Liver Diseases.Molecules and cells · 2020Review
- Neutral Sphingomyelinase-2 (NSM 2) Controls T Cell Metabolic Homeostasis and Reprogramming During Activation.Frontiers in molecular biosciences · 2020Article
- The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
- Sphingolipid changes do not underlie fatty acid-evoked GLUT4 insulin resistance nor inflammation signals in muscle cells.Journal of lipid research · 2018Article
- Cellular Stresses and Stress Responses in the Pathogenesis of Insulin Resistance.Oxidative medicine and cellular longevity · 2018Review
- Sphingolipids in High Fat Diet and Obesity-Related Diseases.Mediators of inflammation · 2015Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChronic metabolic overload leads to insulin resistance in a variety of tissues. It has been shown that exposure to saturated fatty acid palmitate can cause insulin resistance in skeletal muscle cells. Fatty acid induced synthesis of ceramide is considered to be one of the major causes for insulin resistance. Both de novo synthesis and sphingomyelin hydrolysis by sphingomyelinase are implicated for ceramide generation. Aim of this study was to evaluate the impact of neutral sphingomyelinase (nSMase) inhibition on saturated fatty acid induced lipotoxicity and insulin resistance in skeletal muscle myotubes.
resultsTreatment of saturated fatty acid (palmitate) but not unsaturated fatty acid (oleate) caused an up-regulation in expression of various nSMase genes which are associated with ceramide synthesis through the salvage pathway. Inhibition of nSMase by a pharmacological inhibitor (GW4869) partially reverted the palmitate induced insulin resistance in C2C12 myotubes. Inhibition of nSMase improved metabolic functions of myotubes as measured by improved oxidative capacity in terms of increased mitochondrial number, PGC1α expression and ATP levels with concomitant decrease in intramyocellular triglyceride levels. Palmitate induced inflammatory response was also reduced by nSMase inhibitor. GW4869 treatment reduced palmitate induced oxidative and endoplasmic reticulum stress and improved cell survival.
conclusionIn this study, we provide evidences that inhibition of nSMase can protect skeletal muscles from saturated fatty acid induced insulin resistance, metabolic dysfunction, cellular stress and inflammation.
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